BOSTON -- Real and perceived ethical issues in the public's understanding of "organoids" -- miniature, stem-cell derived human organs -- could derail the enormous promise of this new technology unless researchers work proactively to manage them, a panel of scientists in the field said here.
Organoids are expected to become invaluable tools for modeling disease, drug screening, and toxicity testing, as well as being used for therapeutic purposes.
At a special "Focus Session" of the , the organization's ethics committee paired lab scientists and researchers also working in ethics in three areas of the field: organoids generated from adult tissue-specific stem cells, those generated from pluripotent stem cells -- usually by reprogramming adult cells from patients to create personalized organoids -- and the most controversial of the new cellular entities, brain organoids.
Hans Clevers, MD, PhD, of Humbrecht Institute in the Netherlands, led off by discussing one of the first and best understood organoids, mimicking the gut. He said the gut stem cell is "the champion of all stem cells," in that it replaces the entire intestinal lining every four days. He showed images of gut organoids with multiple layers mimicking the natural gut lining, that were infused in rodents trans-anally. They sought out and healed induced lesions. Similarly, gastric organoids have been able to heal Helicobacter-induced lesions in the stomach of rodents.
Noting that organoids were first being developed about four years ago, Clevers said they have now been made for virtually every organ. He added that it is often quite easy to source the starting cells. Lung organoids can be grown from sputum, and bladder and kidney organoids can be made from urine.
Organoids are already being developed by many pharma companies for drug screening and toxicity testing. In an anecdote Clevers shared, one cystic fibrosis patient has already had his therapy determined by a personalized lung organoid made from his cell. Since all the cystic fibrosis drugs on the market are extremely expensive and mutation specific, insurers generally will not pay for treating a patient who does not have the mutation indicated for that drug. This patient's doctor found that his mutation was very close to one of the indicated mutations and when the drug was found to be active in his organoid, the insurer agreed to pay for the drug.
Much of the ethical discussion centered around these commercial applications of organoids, in particular how to verify informed consent for tissue donation for these uses. It was noted that patients view their mini-organs differently -- more emotionally -- than they do cells in a dish. "That is my mini brain" is how panelist Marieke Broekman, MD, PhD, of Harvard Medical School described a common patient reaction to a neural cell organoid, for example.
The stem cell field has long dealt with the ethical issues of creating animal/human chimers, particularly involving brain cells, said Insoo Hyun, PhD, of Case Western Reserve University in Cleveland. Organoid brain work could result in animals much more humanized than cell-based work, he cautioned.
"This is a Dolly the sheep moment," declared Bernard Siegel, JD, of the Regenerative Medicine Foundation, from the audience. "Do they sense pain?" he asked. "This will be seized by anti-science folks."
Hyun acknowledged, "To what extent is creating an organoid creating a person, we need to answer this."